Cellular and Molecular Neurobiology

, Volume 33, Issue 8, pp 1109–1121 | Cite as

14-3-3 Proteins in the Regulation of Rotenone-Induced Neurotoxicity Might be via Its Isoform 14-3-3Epsilon’s Involvement in Autophagy

Original Research


14-3-3 proteins have been confirmed to be involved in Parkinson’s disease. It has been reported that an increase of 14-3-3 (theta, epsilon, and gamma) expression has neuroprotective effect in response to rotenone and MPP+ in dopaminergic cell culture and transgenic C. elegans with alpha-synuclein overexpression. To further investigate the detail mechanism of 14-3-3 proteins in rotenone-induced dopamine neurotoxicity, we observed the expression of 14-3-3 isoforms, and the influence of 14-3-3epsilon knockdown on autophagic activity and cell function. The results showed that rotenone led to a decrease in expression of 14-3-3 protein and mRNA, and an increase in expression and aggregation of alpha-synuclein protein. Knockdown of 14-3-3epsilon expression in turn further aggravated PC12 cell damage, such as an enhancement of ROS formation, and a reduction of cell viability and ATP production. Further experiments confirmed that the autophagic activity was promoted with 14-3-3epsilon siRNA transfection, including an enhancement of autophagosome formation and the ratio of LC3-II/LC3-I. Therefore, we concluded that the regulation of 14-3-3 proteins in rotenone-induced neurotoxicity might be associated with its isoform 14-3-3epsilon’s involvement in autophagy, which might be considered a mechanism in addition to the currently known function of 14-3-3 proteins in neurodegenerative disease pathogenesis.


14-3-3 proteins Rotenone PC12 cells Neurotoxicity Autophagy 



This work was supported by grants from NSFC (Natural Science Foundation of China) (30800932, 81273106) to Yan Sai and Natural Science Foundation of Chongqing (cstc2012jjA10028) to Yan Sai.

Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Yan Sai
    • 1
  • Kaige Peng
    • 1
  • Feng Ye
    • 1
  • Xiaoguang Zhao
    • 2
  • Yuanpeng Zhao
    • 1
  • Zhongmin Zou
    • 1
  • Jia Cao
    • 1
  • Zhaojun Dong
    • 1
  1. 1.The Institute of ToxicologyThird Military Medical UniversityChongqingChina
  2. 2.The Student BrigadeThird Military Medical UniversityChongqingChina

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